Transient activaton of β-catenin signalling in adult mouse epidermis is sufficient to induce new hair follicles but continuous activation is required to maintain hair follicle tumours

When β-catenin signalling is disturbed from mid-gestation onwards lineage commitment is profoundly altered in postnatal mouse epidermis. We have investigated whether adult epidermis has the capacity for β-catenin-induced lineage conversion without prior embryonic priming. We fused N-terminally truncated, stabilised β-catenin to the ligand-binding domain of a mutant oestrogen receptor (ΔNβ -cateninER). ΔNβ-cateninER was expressed in the epidermis of transgenic mice under the control of the keratin 14 promoter and β -catenin activity was induced in adult epidermis by topical application of 4-hydroxytamoxifen (4OHT). Within 7 days of daily 4OHT treatment resting hair follicles were recruited into the hair growth cycle and epithelial outgrowths formed from existing hair follicles and from interfollicular epidermis. The outgrowths expressed Sonic hedgehog, Patched and markers of hair follicle differentiation, indicative of de novo follicle formation. The interfollicular epidermal differentiation program was largely unaffected but after an initial wave of sebaceous gland duplication sebocyte differentiation was inhibited. A single application of 4OHT was as effective as repeated doses in inducing new follicles and growth of existing follicles. Treatment of epidermis with 4OHT for 21 days resulted in conversion of hair follicles to benign tumours resembling trichofolliculomas. The tumours were dependent on continuous activation of β-catenin and by 28 days after removal of the drug they had largely regressed. We conclude that interfollicular epidermis and sebaceous glands retain the ability to be reprogrammed in adult life and that continuous β-catenin signalling is required to maintain hair follicle tumours.Peer reviewedFinal Published versio

Automated Identification and Measurement of Haematopoietic Stem Cells in 3D Intravital Microscopy Data

Image analysis and quantification of Haematopoietic stem cells (HSCs) position within their surrounding microenvironment in the bone marrow is a fast growing area of research, as it holds the key to understanding the dynamics of HSC-niche interactions and their multiple implications in normal tissue development and in response to various stress events. However, this area of research is very challenging due to the complex cellular structure of such images. Therefore, automated image analysis tools are required to simplify the biological interpretation of 3D HSC microenvironment images. In this chapter, we describe how 3D intravital microscopy data can be visualised and analysed using a computational method that allows the automated quantification of HSC position relative to surrounding niche components

The encoding of irrelevance in discourse: tanto between concession and justification

This paper sets out to investigate the linguistic expression of irrelevance in discourse, by focusing on the functions and uses of the marker tanto in present-day Italian. The marker encodes the irrelevance of a given condition, thus conveying a concessive meaning not distant from the value expressed by concessive conditionals or ‘no matter’ predicates. In the construction [p, tanto q], the marker tanto conveys the fact that q holds in any case, namely whether p, non-p,or any value of p is the case. After discussing how the notion of irrelevance has been treated in the literature on condition-als, concessives and predicates of indifference, we will discuss the results of a corpus-based study on spoken Italian, identifying and annotating all the occurrences of irrelevance-tanto. We will show that irrelevance may be expressed by a number of different discourse patterns, explicitly mentioning the irrelevant proposition, the null-effect and the motivation for irrelevance, or omitting one or more of these components. It will be argued that the cases in which speakers simply refer to the irrelevance of a given proposition are rare in our sample, whereas it is more frequent that they also mention the motiva-tion underlying irrelevance, justifying their indifference and thus crucially acting at the intersubjective level. We will show that tanto may also be used alone as a discourse marker encoding the speaker’s attitude of indifference: in these cases, tanto is pronounced with suspensive intonation, and subsumes under its semantics the adversative, justificative, and indiscriminative value, activating meanings that speakers are supposed to share

Conditional connection explored: the case of Sicilian "cusà"

Stemming from a wh-question, the Sicilian marker cusà (cu sa ‘who knows’) expresses several epistemic meanings, which can also reach the realm of conditionality. The paper explores the discourse profile of cusà as it emerges from the analysis of diachronic data (18th-19th centuries) and present-day spoken written Sicilian (web data). These data suggest the possible development path leading from the wh-question to new functions. We propose that the origin of this development can be explained in the light of the strategy of “impossible question”, while the diverse functions of cusà emerged through concomitant processes of desemantisation, reanalysis and subjectification

H2O2 Signature and Innate Antioxidative Profile Make the Difference Between Sensitivity and Tolerance to Salt in Rice Cells

Salt tolerance is a complex trait that varies between and within species. H2O2 profiles as well as antioxidative systems have been investigated in the cultured cells of rice obtained from Italian rice varieties with different salt tolerance. Salt stress highlighted differences in extracellular and intracellular H2O2 profiles in the two cell cultures. The tolerant variety had innate reactive oxygen species (ROS) scavenging systems that enabled ROS, in particular H2O2, to act as a signal molecule rather than a damaging one. Different intracellular H2O2 profiles were also observed: in tolerant cells, an early and narrow peak was detected at 5 min; while in sensitive cells, a large peak was associated with cell death. Likewise, the transcription factor salt-responsive ethylene responsive factor 1 (TF SERF1), which is known for being regulated by H2O2, showed a different expression profile in the two cell lines. Notably, similar H2O2 profiles and cell fates were also obtained when exogenous H2O2 was produced by glucose/glucose oxidase (GOX) treatment. Under salt stress, the tolerant variety also exhibited rapid upregulation of K+ transporter genes in order to deal with K+/Na+ impairment. This upregulation was not detected in the presence of oxidative stress alone. The importance of the innate antioxidative profile was confirmed by the protective effect of experimentally increased glutathione in salt-treated sensitive cells. Overall, these results underline the importance of specific H2O2 signatures and innate antioxidative systems in modulating ionic and redox homeostasis for salt stress tolerance

La traduzione dei nomi nella letteratura per l'infanzia

I nomi propri, che si tratti di antroponimi, di toponimi o di altri tipi di denominazioni, fanno parte di una categoria a sé, benché essi stessi traggano le loro origini dal lessico comune. Essi sono inoltre in grado di offrire ben più di una funzione identificativa, in quanto possono trasmettere tutta una serie di informazioni di tipo anche extra-linguistico sui loro portatori. Si può ad es. desumere con buona approssimazione il periodo in cui un individuo è nato, i gusti dei suoi genitori, la loro confessione religiosa o ideologia politica. Dal cognome si può risalire alla provenienza geografica degli antenati, o anche al loro status sociale. Nomi o cognomi “impegnativi”, quali quello della scrivente, possono aver condizionato, specie in età giovanile, l’atteggiamento del portatore nei confronti della propria stessa identità. Nomi ibridi, cioè che appartengono a lingue e culture diverse, possono essere il segnale di una scissione interiore o aver rappresentato problemi di adattamento. Per quel che riguarda i toponimi, è spesso possibile ricostruire caratteristiche del territorio che possono addirittura essere scomparse, o momenti della storia di un luogo, o ancora l’appartenenza a ben precise tradizioni. Per quel che riguarda i nomi propri che sono calati in un testo letterario, il discorso si complica ulteriormente, perché si presume che ogni nome sia stato scelto dal suo “creatore” in base a ben precise e attente considerazioni, non sempre rintracciabili non solo da parte del lettore, che anzi tende spesso ad ignorarle, bensì anche da parte del critico, che è invece interessato a tutto quel che si nasconde nel retrobottega di un autore. L’onomastica letteraria come disciplina nasce in epoca relativamente recente, non solo in Italia, ma anche a livello internazionale. Maria Giovanna Arcamone, nel suo saggio L’Onomastica letteraria oltralpe, ricostruisce l’itinerario percorso dagli studiosi di onomastica letteraria e individua la data di nascita ufficiale di questo settore di ricerca nel 1970, “quando nella rivista di ICOS “Onoma” venne attivata la sezione bibliografica Literary Onomastics.” Attualmente la ricerca in questo campo viene portata avanti principalmente in Italia grazie all’attività dell’associazione “Onomastica e Letteratura” (=O&L), fondata a Pisa nel 1994, che organizza annualmente un convegno, i cui atti sono regolarmente pubblicati nella rivista “il Nome nel testo”, oltre a curare una collana di studi di onomastica letteraria dal nome Nominatio. Il crescente interesse nei confronti dell’onomastica letteraria ha condotto gli studiosi anche all’approfondimento di singoli aspetti teorici, fra i quali il problema della traduzione dei nomi. Laura Salmon Kovarski, che unisce alla propria attività di ricerca quella di traduttrice di testi dal russo in italiano, è stata, in Italia, nell’ambito dei congressi di O&L, fra i primi, nel 1997, ad affrontare la questione, aprendo la strada ad altri studi riguardanti l’onomastica letteraria in chiave traduttiva, fra i quali il ricco volume Denominazioni proprie e traduzione di Maurizio Viezzi, pubblicato nel non lontano 2010. L’oggetto di questa tesi è costituito appunto dal problema della resa in altre lingue dei nomi propri letterari. Nella prima parte del mio lavoro ho effettuato ricerche e elaborato un Forschungsbericht, individuando trattazioni di linguisti e critici letterari comparse in articoli di riviste, in atti di convegni, in volumi dedicati alla traduzione e alla mediazione culturale. Ho privilegiato le trattazioni che si occupavano prevalentemente di testi tedeschi tradotti in italiano, ma ho preso in considerazione, quando mi è sembrato opportuno, anche contributi in cui si faceva riferimento a testi in lingua inglese, francese e spagnola. Nella seconda parte della tesi ho effettuato una sorta di verifica relativamente alle metodologie e strategie che sono state messe in pratica dai traduttori tedeschi di alcune delle opere di quattro autori italiani che occupano una posizione di rilievo nel campo della letteratura per l’infanzia: Italo Calvino, Gianni Rodari, Luigi Capuana e Mario Lodi

MiR675-5p acts on HIF-1α to sustain hypoxic responses: A new therapeutic strategy for glioma

Hypoxia is a common feature in solid tumours. In glioma, it is considered the major driving force for tumour angiogenesis and correlates with enhanced resistance to conventional therapies, increased invasiveness and a poor prognosis for patients. Here we describe, for the first time, that miR675-5p, embedded in hypoxia-induced long non-coding RNA H19, plays a mandatory role in establishing a hypoxic response and in promoting hypoxia-mediated angiogenesis. We demonstrated, in vitro and in vivo, that miR675-5p over expression in normoxia is sufficient to induce a hypoxic moreover, miR675-5p depletion in low oxygen conditions, drastically abolishes hypoxic responses including angiogenesis. In addition, our data indicate an interaction of miR675-5p, HIF-1α mRNA and the RNA Binding Protein HuR in hypoxia-induced responses. We suggest the modulation of miR675-5p as a new therapeutic option to promote or abolish hypoxia induced angiogenesis

La atenuación a través de la ejemplificación en italiano actual: un estudio basado en corpus

El artículo se refiere a las funciones pragmáticas de la ejemplificación en Italia, centrándose en una serie de construcciones como non so (esp. no sé) y tipo (esp. como). Basándonos en el estudio de tres corpus lingüísticos, podemos hipotetizar que tales construcciones son formalmente heterogéneas. Sin embargo, todas se emplean para expresar atenuación. De hecho, estas se podrían concebir como procedimientos para conceptualizar actos pragmáticos con distinta fuerza ilocutiva, o sea como ejemplos de una amplia serie que tiene el fin de no imponer ni debilitar la carga de compromiso del hablante.The paper addresses the pragmatic functions of exemplification in Italian by focusing on a set of exemplifying constructions such as non so (Eng. ‘I don’t know’) and tipo (Eng. ‘like’). Based on a corpus-based study, we may hypothesise that such constructions may be formally heterogeneous but all of them are employed to express mitigation. Indeed, they may be conceived as procedural tools to conceptualise pragmatic acts with different illocutionary force as examples of a wider set in order not to impose or to weaken the burden of speaker’s commitment.The research described in this paper has been conducted within the SIR program (SIR project «LEAdhoC: The linguistic expression of ad hoc categories», prot. RBSI14IIG0), coordinated by Caterina Mauri

Lettere mercantili tra tracce di oralità e funzioni pragmatiche

The paper sets out to explore twenty-six letters written in Catalan between the XV and the XVI century and sent to Cagliari from Valencia by Pere Martí, a merchant involved in cloth trade around the west Mediterranean area. I will study the letters under examination by seeking to explore their intrinsic discourse and pragmatic dimension. Indeed, in spite of their being written, the letters display special properties that are typical of spoken discourse. In the light of this, I identified various pragmatic functions and properties; among them one can find: employment of address terms with both textual and phatic function, conversational routines such as dislocations, reformulations, parentheticals and polyfunctional connectives. Therefore, along with constituting an important source to reconstruct traits of social and economic history around the west Mediterranean area, the letters under examination are crucial sources to apply the lens of discourse and pragmatic studies to written diachronic texts.Il presente articolo si prefigge di analizzare un insieme costituito da ventisei lettere di argomento mercantile prodotte in lingua catalana a Valenza tra il XV e il XVI secolo e spedite a Cagliari da parte di Pere Martí, mercante di stoffe e manufatti. Intendiamo analizzare caratteristiche e operazioni squisitamente pragmatiche e discorsive alla luce di una prospettiva che considera tali prodotti scrittori come esempi di scrittura intrisa di tratti di oralità. Le lettere sembrano attestare una scrittura che mostra diversi tratti di oralità spesso correlati con l’espressione di sollecitazioni osservabili e ascrivili a funzioni eminentemente pragmatiche rintracciabili nel medium parlato. Diverse sono le strategie pragmatiche osservate: allocutivi con funzione testuale e fàtica, dislocazioni, riformulazioni, parentetici e connettivi polifunzionali – tra altre proprietà. Pertanto, oltre a fornire uno spaccato della storia sociale ed economica a livello delle sponde del Mediterraneo occidentale, le lettere mercantili in esame costituiscono un laboratorio linguistico per applicare approcci di pragmatica e analisi del discorso nel merito di un insieme di testi scritti

A data-driven model on the thermal transfer mechanism of composite phase change materials

Phase change materials (PCMs) that are incorporated with highly conductive nanomaterials to fabricate composite phase change materials (CPCMs), received much focus as a promising energy strategy for latent heat storage and conversion systems, due to their excellent thermophysical properties such as oxidation resistance and large enthalpies of fusion. However, the correct prediction of the thermal conductivity of these CPCMs remains deficient, mainly due to the lack of knowledge on the microscopic heat transfer mechanisms between the nanofiller and matrix interphase. Herein, a data-driven, modified Maxwell model is proposed to determine the thermal conductivity of these CPCMs, using milled carbon fiber (MCF)-reinforced PCMs as validation. This new model incorporates the aspect ratio and morphology smoothness of MCFs and introduces compatibility factors for different types of PCM matrices, which are paraffin and polyethylene glycol (PEG) respectively. At filler loadings above 15 wt%, the theoretical model gave poorer forecasts (with an average prediction error of 0.075) due to the random agglomeration of MCF nanoparticles, which can obstruct the phonon pathway. Regardless, this model accurately estimated the thermal conductivities of MCF/PCMs up to 9 wt% and 11 wt% MCF loading, with percentage fit values being 0.983 and 0.996 for PEG and paraffin systems, respectively. This model also eliminates the limitations of existing models, that were only suitable for composites with low filler loadings